What side effects are associated with this type of intervention?

Common treatments for Acute Myeloid Leukemia (AML) similar to TAS1440 and all-trans retinoic acid (ATRA) can cause a range of side effects. Targeted therapies often result in fatigue, nausea, diarrhea, and cytopenias, which increase the risk of infections and bleeding. ATRA can cause differentiation syndrome, marked by fever, weight gain, respiratory distress, and fluid retention. Additional side effects of ATRA include headache, dry skin, and elevated liver enzymes.

What prior FDA approvals exist?

Several drugs have received FDA approval for the treatment of Acute Myeloid Leukemia (AML), targeting specific pathways in AML cells and promoting differentiation. Hypomethylating agents like azacitidine and decitabine are commonly used and have shown comparable efficacy in treating AML. FLT3 inhibitors such as midostaurin and gilteritinib target mutations in the FLT3 gene, which are common in AML. IDH inhibitors like ivosidenib and enasidenib target mutations in the IDH1 and IDH2 genes, respectively. These treatments, along with the use of all-trans retinoic acid (ATRA) to promote differentiation of immature blood cells, represent a broad spectrum of targeted therapies for AML.

What other types of research exist?

Promising novel alternatives to TAS1440 in combination with ATRA for AML treatment include: 1) JAK1 inhibitors combined with ATRA, which have shown potential in promoting myeloid differentiation and reducing leukemic expansion. 2) Arsenic trioxide (ATO) combined with ATRA, which has been effective in suppressing FLT3-ITD expression and promoting differentiation. 3) Bis-indols like ST1346, which enhance the cytodifferentiating properties of ATRA, improving its efficacy in AML treatment.

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Histone Deacetylase Inhibitor

TAS1440 + ATRA for Leukemia

Phase 1

Waitlist Available

Research Sponsored by Taiho Oncology, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Have an Eastern Cooperative Oncology Group (ECOG) Performance status of 0 to 1.

Women of child-bearing potential (according to recommendations of the Clinical Trial Facilitation Group [CTFG]) must not be pregnant or breastfeeding and must have a negative pregnancy test at screening.

Must not have

Total serum bilirubin ≥1.5 × ULN (except for subjects with Gilbert's Syndrome for whom direct bilirubin is >2.5 × ULN), or liver cirrhosis, or chronic liver disease Child-Pugh Class B or C.

Diagnosis of acute promyelocytic leukemia (M3 AML or APML or APL).

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new drug called TAS1440, alone and with ATRA, in patients with AML who didn't respond to previous treatments or whose cancer returned. It aims to see how the drug works in the body and if it can help treat the leukemia. Bisantrene, a new drug, has shown positive effects in earlier studies with manageable side effects.

Who is the study for?

This trial is for adults with acute myeloid leukemia (AML) who have not responded to standard treatments or whose disease has returned. They should be in a condition stable enough to complete at least one treatment cycle, have an acceptable level of organ function, and women must not be pregnant or breastfeeding. People with certain heart conditions, active infections, other cancers needing treatment, or those unable to take oral medication cannot join.

What is being tested?

The study is testing TAS1440 alone and combined with ATRA in people with relapsed/refractory AML. It aims to evaluate the safety and effectiveness of these treatments over approximately 30 months. Participants will receive TAS1440 as a single agent first then in combination with ATRA.

What are the potential side effects?

Potential side effects may include reactions related to the immune system's response to the drugs, liver and kidney function changes, digestive issues due to oral intake of medication, possible heart complications from pre-existing conditions exacerbated by treatment.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am fully active or restricted in physically strenuous activity but can do light work.

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I am not pregnant or breastfeeding and my pregnancy test was negative.

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My kidney function is within the normal range.

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My cancer did not respond to the initial standard chemotherapy.

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My condition did not improve after treatment with a specific medication.

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My condition worsened after treatment with anthracycline, cytarabine, or a stem cell transplant.

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My AML diagnosis is confirmed and all other treatments have failed.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My bilirubin levels are high, or I have severe liver disease.

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I have been diagnosed with a specific type of leukemia called acute promyelocytic leukemia.

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I have heart problems that significantly limit my daily activities.

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My white blood cell count is over 20,000 due to AML.

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I have severe graft versus host disease needing treatment.

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I cannot swallow pills.

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My leukemia is BCR-ABL positive.

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My leukemia has spread to my brain.

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I need more than 2 liters per minute of oxygen for a lung condition not related to AML.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: TAS1440 + ATRAExperimental Treatment1 Intervention

TAS1440 administered QD on specific days during each 28-day cycle in combination with ATRA twice daily (BID) in Part 2.

Group II: TAS1440Experimental Treatment1 Intervention

TAS1440 as a single agent administered once daily (QD) on specific days during each 28-day cycle in Part 1.

0 / 16Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Acute Myeloid Leukemia (AML) include chemotherapy agents like cytarabine and anthracyclines, which work by damaging the DNA of rapidly dividing cells, leading to cell death. Targeted therapies, such as FLT3 inhibitors, block specific proteins that promote cancer cell growth. All-trans retinoic acid (ATRA) promotes the differentiation of immature blood cells into mature blood cells, which is particularly effective in certain subtypes of AML. The combination of TAS1440, likely targeting specific pathways in AML cells, with ATRA, aims to both inhibit cancer cell proliferation and promote their maturation. Understanding these mechanisms is crucial for AML patients as it helps tailor treatments to target the specific abnormalities in their leukemia cells, potentially improving outcomes and reducing side effects.

Arsenic trioxide and all-trans retinoic acid suppress the expression of FLT3-ITD.A functionally active RARalpha nuclear receptor is expressed in retinoic acid non responsive early myeloblastic cell lines.